text: Hydrolysis of GTP bound to an (active) G domain-GTPase leads to deactivation of the signaling/timer function of the enzyme. The hydrolysis of the third (γ) phosphate of GTP to create guanosine diphosphate (GDP) and P, inorganic phosphate, occurs by the S2 mechanism (see nucleophilic substitution) via a pentacoordinate transition state and is dependent on the presence of a magnesium ion Mg.
  GTPase activity serves as the shutoff mechanism for the signaling roles of GTPases by returning the active, GTP-bound protein to the inactive, GDP-bound state. Most "GTPases" have functional GTPase activity, allowing them to remain active (that is, bound to GTP) only for a short time before deactivating themselves by converting bound GTP to bound GDP. However, many GTPases also use accessory proteins named GTPase-activating proteins or GAPs to accelerate their GTPase activity. This further limits the active lifetime of signaling GTPases. Some GTPases have little to no intrinsic GTPase activity, and are entirely dependent on GAP proteins for deactivation (such as the ADP-ribosylation factor or ARF family of small GTP-binding proteins that are involved in vesicle-mediated transport within cells).
  To become activated, GTPases must bind to GTP. Since mechanisms to convert bound GDP directly into GTP are unknown, the inactive GTPases are induced to release bound GDP by the action of distinct regulatory proteins called guanine nucleotide exchange factors or GEFs. The nucleotide-free GTPase protein quickly rebinds GTP, which is in far excess in healthy cells over GDP, allowing the GTPase to enter the active conformation state and promote its effects on the cell. For many GTPases, activation of GEFs is the primary control mechanism in the stimulation of the GTPase signaling functions, although GAPs also play an important role. For heterotrimeric G proteins and many small GTP-binding proteins, GEF activity is stimulated by cell surface receptors in response to signals outside the cell (for heterotrimeric G proteins, the G protein-coupled receptors are themselves GEFs, while for receptor-activated small GTPases their GEFs are distinct from cell surface receptors).
  Some GTPases also bind to accessory proteins called guanine nucleotide dissociation inhibitors or GDIs that stabilize the inactive, GDP-bound state.
  The amount of active GTPase can be changed in several ways: 
  # Acceleration of GDP dissociation by GEFs speeds up the accumulation of active GTPase. 
  # Inhibition of GDP dissociation by guanine nucleotide dissociation inhibitors (GDIs) slows down accumulation of active GTPase. 
  # Acceleration of GTP hydrolysis by GAPs reduces the amount of active GTPase. 
  # Artificial GTP analogues like GTP-γ-S, β,γ-methylene-GTP, and β,γ-imino-GTP that cannot be hydrolyzed can lock the GTPase in its active state.
  # Mutations (such as those that reduce the intrinsic GTP hydrolysis rate) can lock the GTPase in the active state, and such mutations in the small GTPase Ras are particularly common in some forms of cancer.